Biopolymers such as sugar chain, glycoprotein, glycopeptide, peptide, oligopeptide, protein, nucleic acid, lipid and so forth have key roles in the field of biotechnology including medical science, cell engineering, organ engineering and so forth, so that it has been understood that elucidation of mechanisms of control of biological reactions by these substances may contribute to advancement in the field biotechnology.
Among others, sugar chain is a group of substances highly versatile, and correlated to various functions owned by naturally-occurred lives. The sugar chain often exists in vivo in a form of glycoconjugate while being bound with protein and lipid, known as one of important constituents of biological body. It has increasingly been made clear that the sugar chain is deeply correlated to in vivo regulation of intercellular communication, and function and interaction of proteins.
Note that the sugar chain herein is a general term for molecules configured by monosaccharides such as glucose, galactose, mannose, fucose, xylose, N-acetylglucosamine, N-acetylgalactosamine and sialic acid, or derivatives of these monosaccharides, bound with each other via glycosidic bonds to give a chain.
Biopolymers having the sugar chain may be exemplified by proteoglycans composing plant cells contributive to stabilization of the cells; glycolipids affective to differntiation, proliferation, adhesion, migration and so forth of cells; and glycoproteins correlated to intercellular interaction and cell recognition. Mechanisms of sophisticated and precise control of the sugar chain contained in these biopolymers, based on functional substitution, assistance, amplification, regulation or inhibition with respect to the biopolymers, have increasingly been made clear. If correlations of the sugar chain with differentiation, proliferation, cell adhesion, immunity and neoplastic transformation are further revealed, it is expected to carry out new development by linking this sugar chain engineering to medical science, cell engineering or organ engineering.
In glycoprotein drugs, the sugar chain often plays an important role typically in expression of bioactivity. Accordingly, evaluation of the sugar chain, as a parameter of quality control of the glycoprotein drugs, is extremely important. In particular in the field of antibody drugs, since it was reported that structure of the sugar chain determines antibody dependent cellular cytotoxicity (ADCC activity), the structural analysis of the sugar chain has increasingly added its importance.
Accordingly, techniques of analyzing the sugar chain structure in a rapid, simple and precise manner have recently been desired, and the sugar chain analyses are conducted by a wide variety of methods including high-performance liquid chromatography (HPLC), nuclear magnetic resonance, capillary electrophoresis (CE method), mass analysis, lectin array method and so forth.
For the sugar chain analyses making use of these techniques, it is necessary to preliminarily isolate and purify the sugar chain from proteins, peptides, lipids, nucleic acids and so forth contained in a biological sample. Although HPLC and CE have widely been adopted by virtue of their excellent resolution, good reproducibility, good quantification, and high sensitivity, it is necessary to preliminarily label the reducing end of the sugar chain typically by reductive amination, for the purpose of obtaining high sensitivity. Such purification and labeling of the sugar chain however, requires time and numbers of processes, so that it is difficult to prepare a large amount of samples at a time.
A technique of solving the above-described problem may be exemplified by a method of preparing a sample embodied by using a specific sugar-trapping substance, typically described in Patent Document 1.
[Patent Document 1] WO 2008/018170